- Laboratory values in Japanese children with newly diagnosed inflammatory bowel disease. [Journal Article]
- PIPediatr Int 2019 May 18
- CONCLUSIONS: Percentages of Japanese children with IBD showing normal values at diagnosis mostly resembled Western reports. In early-onset cases, UC values may be similar to CD. Among the 5 tests, we found ESR particularly indicative of disease activity at diagnosis in both pediatric UC and CD. This article is protected by copyright. All rights reserved.
- PET Imaging of [11 C]Rosuvastatin Hepatic Concentrations and Hepatobiliary Transport in Humans in the Absence and Presence of Cyclosporine A. [Journal Article]
- CPClin Pharmacol Ther 2019 May 18
- Using positron emission tomography (PET) imaging, we determined the hepatic concentrations and hepatobiliary transport of [11 C]rosuvastatin (IV injection) in the absence (n=6) and presence (n=4 of 6…
Using positron emission tomography (PET) imaging, we determined the hepatic concentrations and hepatobiliary transport of [11 C]rosuvastatin (IV injection) in the absence (n=6) and presence (n=4 of 6) of cyclosporine A (CsA, IV infusion) following a therapeutic dose of unlabeled rosuvastatin (RSV) (5 mg, PO) in healthy human volunteers. The sinusoidal uptake, sinusoidal efflux and biliary efflux clearance (mL/min) of [11 C]rosuvastatin, estimated through compartment modeling were 1205.6±384.8, 16.2±11.2 and 5.1±1.8, respectively (n=6). CsA (blood concentration: 2.77±0.24 μM), an organic-anion-transporting polypeptide (OATP), Na+ -taurocholate cotransporting polypeptide (NTCP) and breast cancer resistance protein (BCRP) inhibitor increased [11 C]rosuvastatin systemic blood exposure (45%, p<0.05), reduced its biliary efflux clearance (52%, p<0.05) and hepatic uptake (25%, p>0.05) but didn't affect its distribution into the kidneys. CsA increased plasma concentrations of coproporphyrin I and III and total bilirubin by 297±69%, 384±102% and 81±39%, respectively (p<0.05). These data can be used in the future to verify predictions of hepatic concentrations and hepatobiliary transport of rosuvastatin. This article is protected by copyright. All rights reserved.
- Risk of Developing Additional Immune-Mediated Manifestations: A Retrospective Matched Cohort Study. [Journal Article]
- ATAdv Ther 2019 May 17
- CONCLUSIONS: This study demonstrates that the risk of developing a second IMID is significantly higher for individuals who have already experienced a first IMID in a large and contemporary US claims database. Certain pairs of IMIDs co-occur more frequently than others. The risk of developing subsequent IMIDs may be an important consideration for clinicians when selecting treatment strategies.
- Rifamycin SV exhibits strong anti-inflammatory in vitro activity through pregnane X receptor stimulation and NFκB inhibition. [Journal Article]
- DMDrug Metab Pharmacokinet 2019 Jan 17
- Rifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. Rifamycin has …
Rifamycin SV (rifamycin), is a member of the ansamycin family of antimicrobial compounds which kills bacteria commonly associated with infectious diarrhea and other enteric infections. Rifamycin has been found to be effective in experimental animal models of gut inflammation and its efficacy in these settings has been attributed partially to immunomodulatory non-bactericidal activities. This study aimed to further evaluate the anti-inflammatory activities of rifamycin by analyzing its effect on two key regulators of inflammation: PXR and NFκB. Rifamycin stimulated PXR transcriptional activity in two PXR reporter cell lines and induced expression of two genes known to be regulated by PXR and are directly involved in cellular detoxification: CYP3A4 and PgP. Moreover, CYP3A4 metabolic activity was induced by rifamycin in HepG2 cells. Rifamycin also antagonized TNFα and LPS-induced NFκB activities and inhibited IL1β-induced synthesis of inflammatory chemokine, IL8. Although reciprocal regulation of PXR and NFkB by rifamycin was not directly addressed, the data suggest that in the absence of PXR, inhibition of NFκB by rifamycin is not dependent on PXR stimulation. Thus, rifamycin exhibits potent anti-inflammatory activities, characterized by in vitro PXR activation and concomitant CYP3A4 and PgP induction, in parallel with potent NFκB inhibition and concomitant IL8 inhibition.
- Improving the quality of care for people with inflammatory bowel disease (IBD): results of a national audit. [Journal Article]
- FHFuture Hosp J 2015 Jun 01; 2(Suppl 2):s11
- Effects of Vedolizumab in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Diseases. [Journal Article]
- CGClin Gastroenterol Hepatol 2019 May 14
- CONCLUSIONS: In an analysis of patients with PSC and IBD in an international study group, we found no evidence for a biochemical response to vedolizumab, although serum level of ALP decreased by 20% or more in a subset of patients. Vedolizumab appears to be well tolerated and the overall response of IBD was the same as expected for patients without PSC.
- A Real-World Analysis of Prescribing Patterns and Non-persistence of Anti-TNFα Therapy for Inflammatory Bowel Disease. [Journal Article]
- CDClin Drug Investig 2019 May 16
- CONCLUSIONS: The use of anti-TNFα therapy was seen to be low, with a high rate of non-persistence. Further research efforts are required to improve the response rate and, therefore, improve persistence in patients with IBD.
- Extraintestinal Manifestations of Inflammatory Bowel Disease: Epidemiology, Etiopathogenesis, and Management. [Review]
- CGCurr Gastroenterol Rep 2019 May 16; 21(7):31
- Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) represent a complex array of disease processes with variable epidemiologic penetrance, genetic antecedents, and phenotypic pr…
Extraintestinal manifestations (EIMs) of inflammatory bowel disease (IBD) represent a complex array of disease processes with variable epidemiologic penetrance, genetic antecedents, and phenotypic presentations. The purpose of this review is to provide an overview of primary and secondary EIMs as well as salient treatment strategies utilized.
- PROCESS AND SYSTEMS: A population-based model of care for people with inflammatory bowel disease - patient-reported outcomes. [Journal Article]
- FHFuture Healthc J 2019; 6(1):30-35
- The NHS was not designed to provide ongoing support for people with long-term conditions. Conventional outpatient care relies on a diary-based appointment system, with regular follow-up offered to pa…
The NHS was not designed to provide ongoing support for people with long-term conditions. Conventional outpatient care relies on a diary-based appointment system, with regular follow-up offered to patients with a chronic disorder, not always tailored to clinical need. In contrast, at East Surrey Hospital, open access to the inflammatory bowel disease (IBD) service through telephone, email and a web-based portal known as Patients Know Best is offered to all people with IBD, putting them at the centre of the care pathway. This guides and directs those with the greatest clinical need to the clinician with the most appropriate clinical expertise to provide high quality consistent care. Over a 3 month period in 2015, the service avoided 20 hospital admissions, 34 emergency department attendances and 110 outpatient appointments. There is a demonstrable improvement in perception of IBD control and in the patient activation measure, with 66% of those who have used the open access service demonstrating medium to high levels of activation, compared with 11% in those new to the service.
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- A Metagenomic Meta-analysis Reveals Functional Signatures of Health and Disease in the Human Gut Microbiome. [Journal Article]
- MmSystems 2019 Jul-Aug; 4(4)
- While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical …
While recent research indicates that human health is affected by the gut microbiome, the functional mechanisms that underlie host-microbiome interactions remain poorly resolved. Metagenomic clinical studies can address this problem by revealing specific microbial functions that stratify healthy and diseased individuals. To improve our understanding of the relationship between the gut microbiome and health, we conducted the first integrative functional analysis of nearly 2,000 publicly available fecal metagenomic samples obtained from eight clinical studies. We identified characteristics of the gut microbiome that associate generally with disease, including functional alpha-diversity, beta-diversity, and beta-dispersion. Using regression modeling, we identified specific microbial functions that robustly stratify diseased individuals from healthy controls. Many of these functions overlapped multiple diseases, suggesting a general role in host health, while others were specific to a single disease and may indicate disease-specific etiologies. Our results clarify potential microbiome-mediated mechanisms of disease and reveal features of the microbiome that may be useful for the development of microbiome-based diagnostics. IMPORTANCE The composition of the gut microbiome associates with a wide range of human diseases, but the mechanisms underpinning these associations are not well understood. To shift toward a mechanistic understanding, we integrated distinct metagenomic data sets to identify functions encoded in the gut microbiome that associate with multiple diseases, which may be important to human health. Additionally, we identified functions that associate with specific diseases, which may elucidate disease-specific etiologies. We demonstrated that the functions encoded in the microbiome can be used to classify disease status, but the inclusion of additional patient covariates may be necessary to obtain sufficient accuracy. Ultimately, this analysis advances our understanding of the gut microbiome functions that constitute a healthy microbiome and identifies potential targets for microbiome-based diagnostics and therapeutics.